H-Y Antigen and Homosexuality in Men

In men, sexual orientation correlates with the number of older brothers, each additional older brother increasing the odds of homosexuality by approximately 33%. It is hypothesized that this fraternal birth order effect reflects the progressive immunization of some mothers to Y-linked minor histocompatibility antigens (H-Y antigen) by each succeeding male fetus, and the concomitantly increasing effects of H-Y antibodies on the sexual differentiation of the brain in each succeeding male fetus. This hypothesis is consistent with a variety of evidence, including the apparent irrelevance of older sisters to the sexual orientation of later-born males, the probable involvement of H-Y antigen in the development of sex-typical traits, and the detrimental effects of immunization of female mice to H-Y antigen on the reproductive performance of subsequent male offspring.